Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Betaine improves METH-induced depressive-like behavior and cognitive impairment by alleviating neuroinflammation via NLRP3 inflammasome inhibotion","authors":"","doi":"10.1016/j.pnpbp.2024.111093","DOIUrl":"10.1016/j.pnpbp.2024.111093","url":null,"abstract":"<div><p>Methamphetamine abuse has been associated with central nervous system damage, contributing to the development of neuropsychiatric disorders such as depressive-like behavior and cognitive impairment. With the escalating prevalence of METH abuse, there is a pressing need to explore effective therapeutic interventions. Thus, the objective of this research was to investigate whether betaine can protect against depressive-like behavior and cognitive impairment induced by METH. Following intraperitoneal injections of METH in mice, varying doses of betaine were administered. Subsequently, the behavioral responses of mice and the impact of betaine intervention on METH-induced neural damage, synaptic plasticity, microglial activation, and NLRP3 inflammatory pathway activation were assessed. Administration 30 mg/kg and 100 mg/kg of betaine ameliorated METH-induced depressive-like behaviors in the open field test, tail suspension test, forced swimming test, and sucrose preference test and cognitive impairment in the novel object recognition test and Barnes maze test. Moreover, betaine exerted protective effects against METH-induced neural damage and reversed the reduced synaptic plasticity, including the decline in dendritic spine density, as well as alterations in the expression of hippocampal PSD95 and Synapsin-1. Additionally, betaine treatment suppressed hippocampal microglial activation induced by METH. Likewise, it also inhibited the activation of the hippocampal NLRP3 inflammasome pathway and reduced IL-1β and TNF-α release. These results collectively suggest that betaine's significant role in mitigating depressive-like behavior and cognitive impairment resulting from METH abuse, presenting potential applications in the prevention and treatment of substance addiction.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil/lymphocyte ratio and cognitive performances in first-episode patients with schizophrenia and healthy controls","authors":"","doi":"10.1016/j.pnpbp.2024.111092","DOIUrl":"10.1016/j.pnpbp.2024.111092","url":null,"abstract":"<div><p>Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine as a mood stabiliser for schizoaffective disorder: Effectiveness during a three-month follow-up","authors":"","doi":"10.1016/j.pnpbp.2024.111090","DOIUrl":"10.1016/j.pnpbp.2024.111090","url":null,"abstract":"<div><p>Clozapine has shown signs of effectiveness in treating symptoms of schizoaffective disorder, although little research has been carried out to specifically assess this question. The objective of this current work was to analyse the mood-stabilising effectiveness and tolerability of clozapine in patients with schizoaffective disorder.</p><p>This was a prospective, longitudinal, and quasi-experimental trial with three months of follow-up in patients with refractory schizoaffective disorder (PANSS score exceeding 80). Clinical response was evaluated through monthly visits using the YMRS, MADRS, CDSS, CGI-S and UKU. Twenty-seven participants (63% men, 37% women) with a mean age of 32.56 years were included.</p><p>Clozapine significantly reduced the symptoms of mania, as measured by the YMRS (pre-treatment: 16.19, post-treatment: 0.67; <em>p</em> &lt; 0.01) as well as the symptoms of depression, quantified with the CDSS (pre-treatment: 6.11, post-treatment: 0.67; <em>p</em> &lt; 0.01), MADRS (pre-treatment: 9.56, post-treatment: 1.07; <em>p</em> &lt; 0.01), and CGI-S (pre-treatment: 4.74, post-treatment: 1.15; <em>p</em> &lt; 0.01). The prescription of clozapine significantly reduced the average daily dose of neuroleptics, measured in mg of chlorpromazine (pre-treatment: 1253.55, post-treatment: 742.59; <em>p</em> &lt; 0.01) and hypnosedatives, measured in mg of diazepam (pre-treatment: 33.88, post-treatment: 5.74; <em>p</em> &lt; 0.05) required in these patients. Patient-perceived tolerability, measured with the UKU, also improved during follow-up (pre-treatment: 12.89, post-treatment: 8.14; <em>p</em> &lt; 0.01).</p><p>The efficacy of clozapine was significant for the affective symptoms of schizoaffective disorder, thereby improving patient tolerability and permitting reductions in the other medications the patients used.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0278584624001581/pdfft?md5=2403b72fbbfbf36ad8a84b708c8f393b&pid=1-s2.0-S0278584624001581-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder","authors":"","doi":"10.1016/j.pnpbp.2024.111087","DOIUrl":"10.1016/j.pnpbp.2024.111087","url":null,"abstract":"<div><h3>Introduction</h3><p>Anomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD.</p></div><div><h3>Methods</h3><p>Participants included 113 youth, 13–20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses.</p></div><div><h3>Results</h3><p>ROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (<em>p</em> <em>&lt;</em> <em>0.001</em>). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (<em>p</em> <em>&lt;</em> <em>0.001</em>), left thalamus (<em>p</em> <em>&lt;</em> <em>0.001</em>), and right frontal pole (<em>p</em> <em>=</em> <em>0.006</em>). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC.</p></div><div><h3>Conclusion</h3><p>We found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0278584624001556/pdfft?md5=c93381a613f8b9692eb1083072bee62e&pid=1-s2.0-S0278584624001556-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.pnpbp.2024.111089","DOIUrl":"10.1016/j.pnpbp.2024.111089","url":null,"abstract":"<div><h3>Objectives</h3><p>This systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs.</p></div><div><h3>Methods</h3><p>We searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction.</p></div><div><h3>Results</h3><p>Twenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data's quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies.</p></div><div><h3>Conclusion</h3><p>Our results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA dysregulation in glutamate and dopamine pathways of schizophrenia: From molecular pathways to diagnostic and therapeutic approaches","authors":"","doi":"10.1016/j.pnpbp.2024.111081","DOIUrl":"10.1016/j.pnpbp.2024.111081","url":null,"abstract":"<div><p>Schizophrenia is a complex psychiatric disorder, and genetic and environmental factors have been implicated in its development. Dysregulated glutamatergic and dopaminergic transmission pathways are involved in schizophrenia development. Besides genetic mutations, epigenetic dysregulation has a considerable role in dysregulating molecular pathways involved in schizophrenia. MicroRNAs (miRNAs) are small, non-coding RNAs that target specific mRNAs and inhibit their translation into proteins. As epigenetic factors, miRNAs regulate many genes involved in glutamate and dopamine signaling pathways; thereby, their dysregulation can contribute to the development of schizophrenia. Secretion of specific miRNAs from damaged cells into body fluids can make them one of the ideal non-invasive biomarkers in the early diagnosis of schizophrenia. Also, understanding the molecular mechanisms of miRNAs in schizophrenia pathogenesis can pave the way for developing novel treatments for patients with schizophrenia. In this study, we reviewed the glutamatergic and dopaminergic pathophysiology and highlighted the role of miRNA dysregulation in schizophrenia development. Besides, we shed light on the significance of circulating miRNAs for schizophrenia diagnosis and the recent findings on the miRNA-based treatment for schizophrenia.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal stress modulates glutamatergic functional connectivity: A post-synaptic density immediate early gene-based network analysis.","authors":"Licia Vellucci, Giuseppe De Simone, Sara Morley-Fletcher, Elisabetta Filomena Buonaguro, Camilla Avagliano, Annarita Barone, Stefania Maccari, Felice Iasevoli, Andrea de Bartolomeis","doi":"10.1016/j.pnpbp.2024.111032","DOIUrl":"10.1016/j.pnpbp.2024.111032","url":null,"abstract":"<p><p>Early life stress may induce synaptic changes within brain regions associated with behavioral disorders. Here, we investigated glutamatergic functional connectivity by a postsynaptic density immediate-early gene-based network analysis. Pregnant female Sprague-Dawley rats were randomly divided into two experimental groups: one exposed to stress sessions and the other serving as a stress-free control group. Homer1 expression was evaluated by in situ hybridization technique in eighty-eight brain regions of interest of male rat offspring. Differences between the perinatal stress exposed group (PRS) (n = 5) and the control group (CTR) (n = 5) were assessed by performing the Student's t-test via SPSS 28.0.1.0 with Bonferroni correction. Additionally, all possible pairwise Spearman's correlations were computed as well as correlation matrices and networks for each experimental group were generated via RStudio and Cytoscape. Perinatal stress exposure was associated with Homer1a reduction in several cortical, thalamic, and striatal regions. Furthermore, it was found to affect functional connectivity between: the lateral septal nucleus, the central medial thalamic nucleus, the anterior part of the paraventricular thalamic nucleus, and both retrosplenial granular b cortex and hippocampal regions; the orbitofrontal cortex, amygdaloid nuclei, and hippocampal regions; and lastly, among regions involved in limbic system. Finally, the PRS networks showed a significant reduction in multiple connections for the ventrolateral part of the anteroventral thalamic nucleus after perinatal stress exposure, as well as a decrease in the centrality of ventral anterior thalamic and amygdaloid nuclei suggestive of putative reduced cortical control over these regions. Within the present preclinical setting, perinatal stress exposure is a modifier of glutamatergic early gene-based functional connectivity in neuronal circuits involved in behaviors relevant to model neurodevelopmental disorders.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect.","authors":"Matti Bock Guldager, Caroline Biojone, Nicole Rodrigues da Silva, Livea Dornela Godoy, Sâmia Joca","doi":"10.1016/j.pnpbp.2024.111029","DOIUrl":"10.1016/j.pnpbp.2024.111029","url":null,"abstract":"<p><p>Cannabidiol (CBD) is a phytocannabinoid devoid of psychostimulant properties and is currently under investigation as a potential antidepressant drug. However, the mechanisms underlying CBD's antidepressant effects are not yet well understood. CBD targets include a variety of receptors, enzymes, and transporters, with different binding-affinities. Neurochemical and pharmacological evidence indicates that both serotonin and BDNF-TrkB signalling in the prefrontal cortex are necessary for the antidepressant effects induced by CBD in animal models. Herein, we reviewed the current literature to dissect if these are independent mechanisms or if CBD-induced modulation of the serotonergic neurotransmission could mediate its neuroplastic effects through subsequent regulation of BDNF-TrkB signalling, thus culminating in rapid neuroplastic changes. It is hypothesized that: a) CBD interaction with serotonin receptors on neurons of the dorsal raphe nuclei and the resulting disinhibition of serotonergic neurons would promote rapid serotonin release in the PFC and hence its neuroplastic and antidepressant effects; b) CBD facilitates BDNF-TRKB signalling, especially in the PFC, which rapidly triggers neurochemical and neuroplastic effects. These hypotheses are discussed with perspectives for new drug development and clinical applications.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of pregnancy on the pharmacokinetics of antiseizure medications: A systematic review and meta-analysis of data from 674 pregnancies.","authors":"Georgios Schoretsanitis, Kristina M Deligiannidis, Nicholas Kasperk, Chiara Theresa Schmidt, Sarah Kittel-Schneider, Peter Ter Horst, Maya Berlin, Elkana Kohn, Eline M P Poels, Deepti Zutshi, Torbjörn Tomson, Olav Spigset, Michael Paulzen","doi":"10.1016/j.pnpbp.2024.111030","DOIUrl":"10.1016/j.pnpbp.2024.111030","url":null,"abstract":"<p><strong>Objective: </strong>Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.</p><p><strong>Methods: </strong>A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.</p><p><strong>Results: </strong>A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10^-3, 95%CI = -16.08 to -8.58 × 10^-3 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10^-3 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10^-3, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.</p><p><strong>Conclusions: </strong>Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early evidence of beneficial and protective effects of Protectin DX treatment on behavior responses and type-1 diabetes mellitus related-parameters: A non-clinical approach.","authors":"Ana Paula Farias Waltrick, Débora Rasec Radulski, Kauê Marcel de Oliveira, Alexandra Acco, Waldiceu Aparecido Verri, Joice Maria da Cunha, Janaina Menezes Zanoveli","doi":"10.1016/j.pnpbp.2024.111028","DOIUrl":"10.1016/j.pnpbp.2024.111028","url":null,"abstract":"<p><p>Protectin DX (PDX), a specialized pro-resolving lipid mediator, presents potential therapeutic applications across various medical conditions due to its anti-inflammatory and antioxidant properties. Since type-1 diabetes mellitus (T1DM) is a disease with an inflammatory and oxidative profile, exploring the use of PDX in addressing T1DM and its associated comorbidities, including diabetic neuropathic pain, depression, and anxiety becomes urgent. Thus, in the current study, after 2 weeks of T1DM induction with streptozotocin (60 mg/kg) in Wistar rats, PDX (1, 3, and 10 ng/animal; i.p. injection of 200 μl/animal) was administered specifically on days 14, 15, 18, 21, 24, and 27 after T1DM induction. We investigated the PDX's effectiveness in alleviating neuropathic pain (mechanical allodynia; experiment 1), anxiety-like and depressive-like behaviors (experiment 2). Also, we studied whether the PDX treatment would induce antioxidant effects in the blood plasma, hippocampus, and prefrontal cortex (experiment 3), brain areas involved in the modulation of emotions. For evaluating mechanical allodynia, animals were repeatedly submitted to the Von Frey test; while for studying anxiety-like responses, animals were submitted to the elevated plus maze (day 26) and open field (day 28) tests. To analyze depressive-like behaviors, the animals were tested in the modified forced swimming test (day 28) immediately after the open field test. Our data demonstrated that PDX consistently increased the mechanical threshold throughout the study at the two highest doses, indicative of antinociceptive effect. Concerning depressive-like and anxiety-like behavior, all PDX doses effectively prevented these behaviors when compared to vehicle-treated T1DM rats. The PDX treatment significantly protected against the increased oxidative stress parameters in blood plasma and in hippocampus and prefrontal cortex. Interestingly, treated animals presented improvement on diabetes-related parameters by promoting weight gain and reducing hyperglycemia in T1DM rats. These findings suggest that PDX improved diabetic neuropathic pain, and induced antidepressant-like and anxiolytic-like effects, in addition to improving parameters related to the diabetic condition. It is worth noting that PDX also presented a protective action demonstrated by its antioxidant effects. To conclude, our findings suggest PDX treatment may be a promising candidate for improving the diabetic condition per se along with highly disabling comorbidities such as diabetic neuropathic pain and emotional disturbances associated with T1DM.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}